Cathepsin B been shown to be involved in cancer progression. We reported an established antibiotic nitroxoline as a potent and selective inhibitor of cathepsin and elucidated its anti-tumor properties in in vitro and in vivo tumor models. Nitroxoline significantly abrogated tumor growth, angiogenesis and metastasis in vivo in LPB fibrosarcoma and MMTV-PyMT breast cancer mouse models. Overall, our results designate nitroxoline as a promising drug candidate for anti-cancer treatment.
COBISS.SI-ID: 3834225
Cathepsin B has an important role in the development and progression of cancer. It is unique among cathepsins in possessing both carboxypeptidase and endopeptidase activities, the the latter being involved in pathological degradation of the extracellular matrix. Its activities are regulated by different means, the most important being its endogenous inhibitors, the cystatins. In cancer this peptidase/inhibitor balance is altered, leading to harmful cathepsin B activity. The latter can be prevented by exogenous inhibitors. They differ in modes of inhibition, size, structure, binding affinity, selectivity, toxicity and bioavailability. In this article, we review the properties and function of endogenous and exogenous cathepsin B inhibitors and indicate their application as possible anticancer agents.
COBISS.SI-ID: 3730545
The research paper describes unusual properties of cysteine carboxypeptidase cathepsin X in malignant processes. It presents molecular targets, degraded by this protease and mechanisms, leading to progression of the disease. Contrary to other lysosomal proteases cathepsin X does not degrade extracellular matrix but promote tumour progression through regulation of integrin receptors, gamma-enolase, chemokine CXCL-12, bradykinin, kallidin, huntingtin and profilin 1. In particular, its role is important when the activity of other proteases is inactivated, in particular of cathepsin B. In this case its expression is increased enabling alternative pathway of tumour proteolysis. This discovery is important if protease inhibitors are used in antitumour therapy.
COBISS.SI-ID: 3650929
Organometalled compounds, including ruthenium, gained a lot of attention as anticancer agents. In this paper we report on clioquinol-ruthenium complex [Ru(eta6-p-cymene)(Cq)Cl] as a potent inhibitor of cathepsin B, a lysosomal cysteine peptidase, involved in tumour cell invasion and metastasis. The structure belongs to derivatives of nitroxoline. Clioquinol-ruthenium complex did not exhibit cytotoxic effects it did, however, significantly reduced their ability for extracellular matrix degradation and invasiveness in two independent cell-based models.
COBISS.SI-ID: 4164977